Over time, breast cancer survivors who received endocrine therapy (ET) experience significant improvement in ET-related symptoms; however, some ET-related long-term effects may persist. These findings were published in Breast Cancer Research and Treatment.

More than 75% of women with breast cancer receive endocrine therapy (ET) for at least 5 years as part of their treatment. Although ET is an effective treatment that improves outcomes, it also impairs quality of life (QOL) for patients receiving the treatment. The most prevalent adverse effects of ET include hot flashes, joint pain, sexual problems, and emotional instability. Some evidence shows these symptoms persist for many years after treatment completion.

The PROs in Breast Cancer Patients Undergoing ET (PRO-BETh) study, conducted in 2009-2011, demonstrated the value of patient-reported outcomes (PROs) in understanding ET toxicity. In that study, survivors undergoing up-front ET with either aromatase inhibitors or tamoxifen, with or without goserelin (Zoladex), completed a comprehensive questionnaire that assessed QOL, including physical side effects and psychosocial burden, in pre- and postmenopausal women receiving ET as part of their breast cancer treatment.

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The PRO-BETh researchers compared the symptom prevalence rates from their study with data from pivotal phase 4 trials. Patient reports indicated that ET-induced symptom levels were significantly higher for most symptoms than physician ratings. The authors concluded that ET toxicity may be underestimated in routine clinical care.

Therefore, the researchers conducted this follow-up study to gain insight into the long-term sequelae of ET. The goal was to determine patient-reported ET-associated toxicity and QOL outcomes for the PRO-BETh study participants 5 to 10 years later.

All breast cancer patients in the PRO-BETh study were recruited at a routine follow-up appointment or via mail after an introductory telephone call. Participants were asked to complete the same questionnaire battery used in the first assessment: Functional Assessment of Cancer Therapy-Breast (FACT-B) and Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES).

The Functional Assessment of Cancer Therapy-Breast and Endocrine Subscale (FACT-B + -ES) is a 36-item assessment using a 5-point Likert scale. Scale responses ranged from 0 (not at all) to 4 (very much).

Of the 436 patients on ET surveyed in the original study, 268 were eligible to participate in the follow-up, at a median period of 8 years (range 6 to 9 years) after treatment. At the time of follow-up, participants were aged 65 years on average, and 90% were postmenopausal.

Compared with responses from the first assessment, follow-up assessment scores showed improvement in overall endocrine symptomatology (59 vs 62; P <.001), physical well-being (23.9 vs 24.8; P <.01), functional well-being (21.7 vs 22.7; P =.013), and overall QOL (88.3 vs 90.9; P =.011).

Vasomotor symptoms decreased significantly with time: hot flashes, 68.7% vs 39.5%; cold sweats, 30.0% vs 16.3%; night sweats, 47.0% vs 24.3%; and sleeping difficulties, 14.9% vs 9.5%.

Gynecologic symptoms did not change over time, except vaginal discharge, which decreased (12.4% vs 4.6%). Loss of interest in sex increased (40.4% vs 48.7%).

Prevalence of symptoms known to be ET-induced were similar over time, including joint pain (45.5% vs 44.2%), lack of energy (36.4% vs 33.8%), weight gain (36.8% vs 33.9%), and vaginal dryness (30.2% vs 33.0%).

These results demonstrate that overall endocrine symptomatology and QOL improved over time in breast cancer survivors who received ET as part of their treatment. But some clinically relevant and unfavorable ET-related effects persist long after treatment completion. The most persistent symptoms reported by survivors were joint pain, lack of energy, and sexual health issues.

“Survivorship care efforts should focus on these problems,” suggested the authors. They also suggested that survivors receive more information on the long-term effects of breast cancer treatments and continued assessment of symptoms as part of individually tailored long-term care plans.


Albertini C, Oberguggenberger A, Sztankay M, et al. Does the toxicity of endocrine therapy persist into long-term survivorship?: patient-reported outcome results from a follow-up study beyond a 10-year-survival. Breast Cancer Res Treat. Published online November 23, 2022. doi:10.1007/s10549-022-06808-9